Anti-parallel membrane topology of a homo-dimeric multidrug transporter, EmrE

J Biochem. 2007 Nov;142(5):621-5. doi: 10.1093/jb/mvm169.

Abstract

EmrE in Escherichia coli belongs to the small multidrug resistance (SMR) transporter family. It functions as a homo-dimer, but the orientation of the two monomers in the membrane (membrane topology) is under debate. We expressed various single-cysteine EmrE mutants in E. coli cells lacking a major efflux transporter. Efflux from cells expressing the P55C or T56C mutant was blocked by the external application of membrane-impermeable SH-reagents. This is difficult to explain by the parallel topology configuration, because Pro55 and Thr56 are considered to be located in the cytoplasm. From both the periplasm and the cytoplasm, biotin-PE-maleimide, a bulky membrane-impermeable SH-reagent, could access the cysteine residue at the 25th position in the presence of transport substrates and at the 108th position. These observations support the anti-parallel topology in the membrane.

MeSH terms

  • Antiporters / chemistry*
  • Antiporters / genetics
  • Antiporters / metabolism
  • Biological Transport
  • Biotin / pharmacology
  • Cell Membrane Permeability
  • Cysteine / genetics
  • Cytoplasm / chemistry
  • Cytoplasm / metabolism*
  • Dimerization
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Maleimides / pharmacology
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Multidrug Resistance-Associated Proteins / chemistry*
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • Mutation
  • Periplasm / chemistry
  • Periplasm / metabolism*
  • Polyethylene / pharmacology
  • Proline / genetics
  • Protein Structure, Secondary
  • Threonine / genetics

Substances

  • Antiporters
  • Escherichia coli Proteins
  • Maleimides
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • EmrE protein, E coli
  • maleimide
  • Threonine
  • Biotin
  • Polyethylene
  • Proline
  • Cysteine